{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:53Z","timestamp":1792789673706,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82272383"],"award-info":[{"award-number":["82272383"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82272383"],"award-info":[{"award-number":["82272383"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hunan Province","award":["2024JJ5341"],"award-info":[{"award-number":["2024JJ5341"]}]},{"name":"Hunan Provincial Health High-Level Talent Scientific Research Project","award":["R2023056"],"award-info":[{"award-number":["R2023056"]}]},{"name":"Key guidance project of Health Commission of Hunan Province","award":["C202304127239"],"award-info":[{"award-number":["C202304127239"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Chlamydia trachomatis (Ct) infection is a major cause of infertility, primarily through inducing tubal fibrosis. Epithelial\u2013mesenchymal transition (EMT) plays a central role in this fibrotic process. However, the molecular mechanisms by which Ct infection triggers EMT are not fully understood. IFN-\u03b3 is a major component of the host immune pressure acting on infected epithelial cells during Ct infection. To mimic this immune environment in vitro and investigate how host signaling responses to Ct infection influence EMT, we maintained Ct-infected HeLa cells under continuous IFN-\u03b3 treatment and examined Wnt\/\u03b2-catenin and Notch signaling. Under this condition, both pathways were activated and exhibited functional crosstalk potentially involving JAG1. Inhibition of either pathway attenuated EMT-associated phenotypes and was associated with reduced infectious progeny production. These findings support a role for Wnt\/\u03b2-catenin\u2013Notch crosstalk in promoting EMT in Ct-infected cells under continuous IFN-\u03b3 treatment.<\/jats:p>","DOI":"10.3390\/microorganisms14092074","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"2074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Wnt\/Notch Crosstalk Promotes Epithelial\u2013Mesenchymal Transition During Chlamydia trachomatis Infection Under IFN-\u03b3 Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5435-8188","authenticated-orcid":false,"given":"Yewei","family":"Yang","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Fang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongrong","family":"Wu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-0936","authenticated-orcid":false,"given":"Yating","family":"Wen","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-3997","authenticated-orcid":false,"given":"Zhongyu","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, Institute of Pathogenic Biology, School of Nursing, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1136\/sextrans-2024-056333","article-title":"Prevalence of chlamydia and gonorrhoea among Kenyan adolescents","volume":"101","author":"Truong","year":"2025","journal-title":"Sex. Transm. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.idc.2023.02.007","article-title":"Update on the Epidemiology, Screening, and Management of Chlamydia trachomatis Infection","volume":"37","author":"Hocking","year":"2023","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1093\/infdis\/jiab031","article-title":"Pelvic Inflammatory Disease Due to Neisseria gonorrhoeae and Chlamydia trachomatis: Immune Evasion Mechanisms and Pathogenic Disease Pathways","volume":"224","author":"Darville","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_4","first-page":"101027","article-title":"Reproductive tract complication risks following Chlamydia trachomatis infections: A long-term prospective cohort study from 2008 to 2022","volume":"45","author":"Alexiou","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.1093\/infdis\/jiab088","article-title":"Is There a Hidden Burden of Disease as a Result of Epigenetic Epithelial-to-Mesenchymal Transition Following Chlamydia trachomatis Genital Tract Infection?","volume":"224","author":"Horner","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Caven, L.T., and Carabeo, R.A. (2023). The role of infected epithelial cells in Chlamydia-associated fibrosis. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1208302"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11010-021-04270-7","article-title":"Fallopian tubal infertility: The result of Chlamydia trachomatis-induced fallopian tubal fibrosis","volume":"477","author":"Ling","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1016\/j.cell.2025.08.033","article-title":"Epithelial-mesenchymal transition","volume":"188","author":"Zhang","year":"2025","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/j.celrep.2019.01.006","article-title":"Integrated Phosphoproteome and Transcriptome Analysis Reveals Chlamydia-Induced Epithelial-to-Mesenchymal Transition in Host Cells","volume":"26","author":"Zadora","year":"2019","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Caven, L.T., Brinkworth, A.J., and Carabeo, R.A. (2023). Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1098420"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Darville, T., Sun, X., Zhang, Y., O\u2019Connell, C.M., Mokashi, N.V., Tang, W., Bhardwaj, A., Duncan, B., Andrews, C.W., and Wiesenfeld, H.C. (2026). miRNA\/mRNA analysis of increased TGF-\u03b2 pathways drive epithelial-mesenchymal transition and regulatory T cell differentiation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1679688"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00904-23","DOI":"10.1128\/msystems.00904-23","article-title":"Chlamydial YAP activation in host endocervical epithelial cells mediates pro-fibrotic paracrine stimulation of fibroblasts","volume":"8","author":"Caven","year":"2023","journal-title":"mSystems"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41392-022-00934-y","article-title":"Notch signaling pathway: Architecture, disease, and therapeutics","volume":"7","author":"Zhou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wen, Y., Luo, F., Zhao, L., Su, S., Lei, W., Liu, Y., Shi, K., and Li, Z. (2021). Long Non-Coding RNA FGD5-AS1 Induced by Chlamydia trachomatis Infection Inhibits Apoptosis via Wnt\/\u03b2-Catenin Signaling Pathway. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.701352"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115124","DOI":"10.1016\/j.biopha.2023.115124","article-title":"Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch\/Jag1 mediated by the Wnt\/\u03b2-catenin pathway","volume":"165","author":"Xiao","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/21505594.2022.2044666","article-title":"LncRNA ZEB1-AS1\/miR-1224-5p\/MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection","volume":"13","author":"Luo","year":"2022","journal-title":"Virulence"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4161\/cc.26951","article-title":"GSI promotes vincristine-induced apoptosis by enhancing multi-polar spindle formation","volume":"13","author":"Singh","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13045-024-01563-4","article-title":"Wnt\/\u03b2-catenin signaling pathway in carcinogenesis and cancer therapy","volume":"17","author":"Song","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eabd7974","DOI":"10.1126\/sciadv.abd7974","article-title":"Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition","volume":"7","author":"Serresi","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/s41467-022-28569-1","article-title":"Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming","volume":"13","author":"Koster","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ekka, R., Gutierrez, A., Johnson, K.A., Tan, M., and S\u00fctterlin, C. (2024). Chlamydia trachomatis induces disassembly of the primary cilium to promote the intracellular infection. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012303"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ajpath.2011.09.015","article-title":"Chlamydia trachomatis Disturbs Epithelial Tissue Homeostasis in Fallopian Tubes via Paracrine Wnt Signaling","volume":"180","author":"Kessler","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"eady1640","DOI":"10.1126\/sciadv.ady1640","article-title":"Single-cell atlas of cervical organoids uncovers epithelial immune heterogeneity and intercellular cross-talk during Chlamydia infection","volume":"11","author":"Prakash","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1128\/IAI.70.5.2605-2613.2002","article-title":"Chlamydia trachomatis Disrupts N-Cadherin-Dependent Cell-Cell Junctions and Sequesters \u03b2-Catenin in Human Cervical Epithelial Cells","volume":"70","author":"Prozialeck","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6720","DOI":"10.1038\/s41388-021-02062-3","article-title":"MCPIP1 inhibits Wnt\/\u03b2-catenin signaling pathway activity and modulates epithelial-mesenchymal transition during clear cell renal cell carcinoma progression by targeting miRNAs","volume":"40","author":"Gorka","year":"2021","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Saran, U., Chandrasekaran, B., Tyagi, A., Shukla, V., Singh, A., Sharma, A.K., and Damodaran, C. (2023). A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth. Front. Pharmacol., 14, Erratum in Front. Pharmacol.\u00a02024, 15, 1420266.","DOI":"10.3389\/fphar.2023.1150774"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"250282","DOI":"10.1098\/rsob.250282","article-title":"Decoding \u2018Wntch\u2019: The intertwined Wnt and Notch pathways in development and disease","volume":"16","author":"Turetti","year":"2026","journal-title":"Open Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41413-024-00342-8","article-title":"Wnt\/\u03b2-catenin signaling components and mechanisms in bone formation, homeostasis, and disease","volume":"12","author":"Hu","year":"2024","journal-title":"Bone Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kintner, J., Moore, C.G., Whittimore, J.D., Butler, M., and Hall, J.V. (2017). Inhibition of Wnt Signaling Pathways Impairs Chlamydia trachomatis Infection in Endometrial Epithelial Cells. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00501"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1038\/s41467-025-63053-6","article-title":"The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/2074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:17:29Z","timestamp":1789791449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/2074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["microorganisms14092074"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14092074","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}